SARS-CoV-2 N Protein mimics MS proteins

And XBB weak pathogenicity

This was the other paper I mentioned and wrote it has similar significance as the last one, and I am glad I had other affairs to attend to because we now have “good news”, I will refer to these later. If you use the search function in Substack and the term “molecular mimicry” you will find many pieces about it, and how I have a huge interest in the topic.

You can read a lot of interesting snippets in the following substack.

The many faces of the Spike Protein of SARS-CoV-2

Sequence similarity between SARS-CoV-2 nucleocapsid and multiple sclerosis-associated proteins provides insight into viral neuropathogenesis following infection

A significant proportion of these sequelae are related to aberrations in the central nervous system (CNS)2. In fact, 1 in 4 individuals with long-COVID recently reported persistent cognitive deficits and there is an emerging consensus on the significance of long-COVID as a public health burden3. Neurological manifestations have also been reported during acute SARS-CoV-2 infection, including encephalitis, encephalomyelitis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, and multiple sclerosis4.

Multiple sclerosis (MS) is the most common autoimmune demyelinating disease in the United States and affects approximately 3 million people worldwide5. It has been widely suggested that the etiology of MS involves an initial infectious insult. For decades, it has been noted that the onset of first and recurring episodes of MS are often preceded by acute infections6,7,8. Importantly, studies investigating seasonal coronaviruses and SARS-CoV-2 have suggested the ability of these viruses to elicit cross-reactivity with viruses thought to play a role in the initial pathogenesis of MS9. In addition, other notable autoimmune diseases such as Guillain–Barre Syndrome, hypothesized to be driven in part by molecular mimicry, have been reported following SARS-CoV-2 infection10. We hypothesized that SARS-CoV-2 proteins share homology with CNS proteins, which could play a role in the physical manifestations of MS following acute SARS-CoV-2 infection.

I am a really huge fan of authors that pull no punches and tell whatever they believe is a viable hypothesis without mincing words. And they are correct, a sizable portion of people afflicted with Long Covid, especially the ones harder to treat/recover often have Central Nervous System related issues, or nerve issues.

One of the drivers of many autoimmune conditions has been stated to be the similarity between the body's own proteins and the proteins of something else (Homology means this).

A 9mer and a 13mer are the numbers of peptides (the letters you see all the time in certain papers). As you can see by the graphics above, the Nucleocapsid Protein (N Protein from here on) had the biggest number of potential mimic sites than the other proteins tested, and these were selected because they are all vital to the virus life cycle and replication. We just covered the importance of the Envelope in regards to the novel method SARS-CoV-2 can travel and infect cells.

In one study, T cell lines derived from MS patients and activated with PLP showed the strongest reactivity against regions 40–60, 95–117, 117–150, and 185–206 out of all 9 regions of PLP tested20. The authors concluded from this study that these regions were largely responsible for eliciting strong T cell responses in MS patients. We found that the PLP peptides returned from PEPMatch fell within one of these immunodominant regions. Overall, these results provide a computational basis for the potential of SARS-CoV-2 to initiate T-cell-driven molecular mimicry through specific MS-associated proteins, including PLP.

The PEPMatch-predicted epitope of PLP matching nucleocapsid (blue) was aligned with the full-length sequence of PLP (black) and the nucleocapsid peptide to which it matches (green) alongside examples of known epitopes of PLP identified in the literature and available on the IEDB (berry).

The focus of the authors on PLP is well founded by the fact that by literature alone, it is one of the proteins mostly linked with MS. PLP is one of the most important proteins that help the formation of the myelin, which is a little “sheath” on top of your nerves when a pathogen or your own antibodies attack it, you can get very serious, severe reactions, and long term damage. It is exactly what I developed an autoinflammatory reaction years ago (I wrote about it here sometime back).

A protein being a mimic or having the correct shape isn’t the only necessary step to develop MS or other autoimmune issues, binding to your immune cells is among the most relevant steps toward such an event. So to further their hypothesis, the authors used the PEPMatch to test the binding of other proteins of interest to MHC, you can read (or watch the very informative video, easy to understand) about MHC in the post down below, basically a crucial part of our immune system.

SARS-CoV-2 ORF8 regulates immune response

Testing if certain alleles (varieties of genes, that can make one more resilient or susceptible to any form of disease or infection), the authors found that other proteins that could trigger autoimmunity in the MS context can happen across a wide range of HLA (MHC) “types”. What is more intriguing was the fact that other seasonal coronaviruses share significant homology with MS-associated proteins, but not with PLP, only PLP had a significant overlap with the N Protein.

Myelin proteolipid protein (PLP) has been implicated in the development of MS across a multitude of studies20,38,39,40. In humans, the development of MS following Rubella virus infection was demonstrated to be linked to the high relative similarity score of E2 protein to PLP16,41, demonstrating the potential for sequence overlap leading to the induction of demyelinating disease.Among the numerous studies that have investigated the autoantigenicity of specific epitopes of PLP in the context of MS-development18,19, certain epitopes have been specifically associated with eliciting strong T cell responses in MS patients20. The epitope returned from PEPMatch in our study, 120–134, is encompassed within an epitope associated with strong T cell responses in DR15*01-positive MS subjects20 . Collectively, this data substantiates the hypothesis that SARS-CoV-2 nucleocapsid may be providing the basis for molecular mimicry preceding the development of MS in susceptible individuals.

The last 3 paragraphs of the paper are rather heavy content-wise but packed with good insights and further reading on the subject, but the relevant section was highlighted.

In genetically susceptible individuals, the N protein and its molecular mimicry might help the development of multiple sclerosis, and further driving the point in these types of individuals, it also may help drive other types of degenerative diseases. Is this a big, apocalyptic problem ? Not really, but it is incredibly important work because if the end of the pandemic and basically the virus losing most of its pathogenicity (so far) we will now have to untangle and deal with the long-term damage of the virus, which I said in 2020 it would eclipse anything even pessimists thought.

Outside the scope of the paper, there are many other highly important aspects to the development and progression of MS, and this one our dear old friend shares much more of the blame than the N protein. The spike and especially outrageously, the mRNA immune response further driven by the Spike Protein share a couple of the most important aspects of the progression of MS. Interleukin-17. Interferon-Gamma, in CD4+ T cells. Which can be modulated by β2-Adrenoreceptor (mark down this one, it will be really important as we go on). (The paper linked is a good reading on this subject, and gives a lot of clues for a subset of Long Covid patients).

From all the research I have done so far (years and years worth), most neurodegenerative diseases share many common pathways, negative feedback loops, and opportunistic pathogens working together, including MS. Therefore a lot of what I recommend to either mitigate or treat any after-effects of a SARS-CoV-2 infection often will also help with said conditions, so I am fairly confident if you take care of your health, mitigate oxidative stress and inflammation as much as possible, take whatever antioxidant you chose, this shouldn’t be a problem.

Stopping or minimizing the inflammatory response and feedback loop is the goal, this stops everything else most of the time.

And as good news, and in relation to the last substack I published.

Inspiration of SARS-CoV-2 envelope protein mutations on 2 pathogenicity of Omicron XBB

In the scope of this research, XBB has further weakened pathogenicity among all Omicron sub-variants, it kills fewer cells, induces less cytokine, and lower viral production, and following the trend since the first Omicron surfaced, weakened lung damage. All of these are by using mutations in the Envelope protein as markers.

Some of the most lethal mutations simply disappear, while others are almost “fixated”, meaning they present in most of the sequences uploaded. One could argue this theoretically diminishes the Envelope Protein effects on generating EVs that carry the virus, of course, this above all else should be tested to further elucidate if certain mutations grant the virus better capacity to create the EVs.

Whatever is killing people isn’t XBB…

The next one will be most recent papers about treatments/supplements I (and others obviously) recommended, and are now proven to work. As anyone who read literature said it would. NAC, Melatonin, Metformin, my favorite trifecta.


And as always, I am thankful for your support, and for sharing what you find helpful.